The Hypothalamic Hamartoma: A Model of Subcortical Epileptogenesis and Encephalopathy

Although uncommon, the hypothalamic hamartoma (HH) is often associated with a devastating clinical syndrome, which may include refractory epilepsy, progressive cognitive decline, and deterioration in behavioral and psychiatric functioning. Contrary to conventional thinking which attributed seizure origin to cortical structures, the hamartoma itself has now been firmly established as the site of intrinsic epileptogenesis for the gelastic seizures (ie, characterized by unusual mirth) peculiar to this disorder. It also appears that the HH contributes to a process of secondary epileptogenesis, with eventual cortical seizure onset of multiple types in some patients. Anticonvulsant medications are known to be poorly effective in this disorder. Treatment, including some innovative approaches to surgical resection, is now targeted directly at the HH itself, with impressive results. Younger patients, in particular, may avoid the deteriorating course described earlier. Access to tissue from larger numbers of patients at single or collaborating centers specializing in HH surgery will allow for research into the fundamental mechanisms producing this little understood disorder. Refractory epilepsy associated with HH is the premier human model for subcortical epilepsy and an excellent model for secondary epileptogenesis and epileptic encephalopathy.